Wound healing is an intricate process in which the skin or another organ or tissue, repairs itself after injury. In normal skin, the epidermis (outermost layer) and dermis (inner or deeper layer) exists in a steady-state equilibrium, forming a protective barrier against the external environment. Once the protective barrier is broken, the normal physiologic process of wound healing is immediately set in motion. The classic model of wound healing is divided into three sequential, yet overlapping phases, namely: inflammatory, proliferative and finally remodelling.
During the inflammatory phase of wound healing there is active recruitment of neutrophils and then monocytes from surrounding vasculature into the wound. Neutrophils are essential to the initial control and destruction of bacterial and fungal infections in the wound. Monocytes mature into macrophages as they enter the wound where they have numerous roles during the course of wound resolution including the initial phagocytosis and clean-up of matrix and cell debris. The release of enzymes, cytokines and growth factors by both neutrophils and macrophages in the wound can then exert a profound influence on other cells within the wound and surrounding tissue. For example, macrophages secrete collagenases which debride the wound; interleukins and tumor necrosis factor (TNF), which stimulate fibroblasts and promote angiogenesis; and transforming growth factor (TGF), which stimulates keratinocytes. They also secrete platelet-derived growth factor and vascular endothelial growth factor which initiate the formation of granulation tissue and thus initiate the transition into the proliferative and remodelling phases. A rapid and robust, but transient, inflammatory phase is often associated with good wound healing outcomes.
The second stage of wound healing involves cell proliferation and migration and wound contraction. This involves actions taken by cells within the wound to achieve closure of the wound gap and replenish lost tissue. Migration and proliferation of keratinocytes is fundamental to achieve re-epithelialisation of the wound, while reconstitution of the underlying dermis results from migration, proliferation and differentiation of fibroblasts which help draw the wound closed and contribute to the synthesis, bundling and alignment of collagen fibres.
In the final remodelling stage, migrating and proliferating keratinocytes at the wound edge re-stratify to seal the wound and form a continuous epidermis. During this stage many changes also occur in the dermis involving remodelling of the extracellular matrix to restore a normal dermal architecture and vasculature.
In certain cases, wounds may be slow to heal or not heal at all. Many factors affect the healing of a wound, for example, the general health of the wounded subject, the age of the wounded subject, diseases such as diabetes, or other diseases that may affect circulation, the presence of infection, foreign objects or necrotic tissue, or in some instances, medication may affect the rate of wound healing.
Furthermore, in some wounds imperfect regulation of wound resolution can result in fibrosis and excessive scar formation to leaving scar tissue that is functionally and cosmetically inferior to normal tissue.
There is much research into improving wound healing and reducing scar tissue. However, there is a need to find agents that are capable of promoting wound healing, for example, increasing the rate of wound healing, particularly in chronic wounds. There is also a need for agents that allow a wound to heal with reduced scarring than would occur naturally.